Heterogeneity in Immune Marker Expression after Acquisition of Resistance to EGFR Kinase Inhibitors: Analysis of a Case with Small Cell Lung Cancer Transformation

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Heterogeneity in Immune Marker Expression after Acquisition of Resistance to EGFR Kinase Inhibitors: Analysis of a Case with Small Cell Lung Cancer Transformation Kenichi Suda, MD, PhD, Isao Murakami, MD, PhD, Hui Yu, MD, PhD, Jihye Kim, PhD, Kim Ellison, MS, Christopher J. Rivard, PhD, Tetsuya Mitsudomi, MD, PhD, Fred R. Hirsch, MD, PhD Journal of Thoracic Oncology Volume 12, Issue 6, Pages 1015-1020 (June 2017) DOI: 10.1016/j.jtho.2017.02.002 Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 1 Comparison of immune marker expression in tumors with T790M mutation versus SCLC transformation. (A) Programmed death ligand 1 (PD-L1) was positively stained by immunohistochemistry (IHC) in a part (5%) of the tumor cells (arrowhead) and stromal cells in liver metastasis with adenocarcinoma (T790M mutation) (original magnification, ×40). (B) PD-L1–negative results in both tumor cells and stromal cells in liver metastasis with SCLC histological transformation (original magnification, ×20). (C–E) Expression of CD8 (left) and PD-1 (right) in liver metastasis with adenocarcinoma/T790M (original magnification, ×10) (C), retroperitoneum lymph node metastasis (SCLC) (original magnification, ×20) (D), and peripancreatic lymph node metastasis (adenocarcinoma/T790M) (original magnification, ×40) (E) are shown. Journal of Thoracic Oncology 2017 12, 1015-1020DOI: (10.1016/j.jtho.2017.02.002) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 2 Results from the Immuno-Oncology expression panel. (A and B) Relative expression of T-cell–inhibitory checkpoint molecules (A) and costimulatory molecules (B) according to the HTG EdgeSeq Immuno-Oncology panel. Expression of each molecule was normalized by comparing the liver metastasis (metast.) with adenocarcinoma (AC). (C) A heatmap analysis of genes with significant changes (false discovery rate <0.05, log fold change >|2|) is shown. Up-regulated and/or down-regulated genes by type I interferon (IFN) were obtained from the Interferome database.10 LN, lymph node; IFI27, interferon alpha inducible protein 27 gene; ISG15, ISG15 ubiquitin-like modifier gene; MUC1, mucin 1, cell surface associated gene; MX1, MX dynamin like GTPase 1 gene; DUSP6, dual specificity phosphatase 6 gene; LIF, leukemia inhibitory factor gene; IFIT2, interferon induced protein with tetratricopeptide repeats 2 gene; CXCL1, C-X-C motif chemokine ligand 1 gene; CASP10, caspase 10 gene; ITGA5, integrin subunit alpha 5 gene; SYK, spleen associated tyrosine kinase gene; L1CAM, L1 cell adhesion molecule gene; SERPINB2, serpin family B member 2 gene; BCL2, BCL2, apoptosis regulator gene; CCL4, C-C motif chemokine ligand 4 gene; FYN, FYN proto-oncogene, Src family tyrosine kinase gene; IL1B, interleukin 1 beta gene; EBF4, early B-cell factor 4 gene; CXCL5, C-X-C motif chemokine ligand 5 gene; HMOX1, heme oxygenase 1 gene; HEY2, hes related family bHLH transcription factor with YRPW motif 2 gene. Journal of Thoracic Oncology 2017 12, 1015-1020DOI: (10.1016/j.jtho.2017.02.002) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions